Genotypic resistance at viral rebound among patients who received lopinavir/ritonavir-based or efavirenz-based first antiretroviral therapy in South Africa.

Office of Clinical Operation, Project Phidisa, South African Military Health Service (SAMHS), Pretoria, South Africa.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.65). 06/2011; 58(3):304-8. DOI: 10.1097/QAI.0b013e3182278c29
Source: PubMed

ABSTRACT Nonnucleoside reverse transcriptase inhibitor-drug resistance mutations (DRM) are increasingly reported in Africans failing their first antiretroviral regimen. The Phidisa II trial randomized treatment-naive participants to lopinavir/ritonavir or efavirenz with stavudine + lamivudine or zidovudine + didanosine. We report the prevalence of DRM in subjects who achieved HIV RNA <400 copies per milliliter at 6 months, but subsequently had 2 consecutive HIV RNA >1000 copies per milliliter. Sixty-eight participants fulfilled the inclusion criteria. nonnucleoside reverse transcriptase inhibitor-DRM were found in 17 of 36 (47.2%) efavirenz recipients, and M184V/I mutation in 14 of 40 (35.0%) lamivudine recipients. No protease inhibitor mutation was identified in 38 lopinavir/ritonavir recipients. This is one of the first studies in Africa confirming the paucity of protease inhibitor-associated DRM despite virologic failure.

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    ABSTRACT: Background Increases in the prevalence of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been observed among previously untreated individuals in all areas of sub-Saharan Africa. We aimed to examine whether first-line use of 2 NRTIs plus a boosted protease inhibitor (bPI) could protect against emergence of NRTI resistance mutations, compared to the use of 2 NRTIs plus 1 NNRTI. Methods We carried out a weighted meta-analysis of randomized clinical trials comparing bPI- with NNRTI-based first-line antiretroviral therapy regimens using random effects modeling. Results In intention to treat analyses, there was no difference in the risk of viral failure at week 48 between NNRTI and bPI (P = .19). At week 48, the overall difference between NNRTI- and PI-based regimens in selection of any major NRTI resistance mutation (crude unweighted prevalence 3.3% vs 1.6%) was 1.7% (95% confidence interval [CI], .4-3.0; P = .00927). There was a statistically significant difference in prevalence of K65R when comparing NNRTI (1.3%) with PI (0.67%); absolute weighted difference 1.0% (95% CI, .3-1.7; P = .00447). There was also a significant difference in prevalence of M184V/I between NNRTI and PI (crude unweighted prevalence 3.2% vs 1.4%); difference 1.6% (95% CI 0.1-3.1; P = .0368). Conclusions Despite the equivalent efficacy and more favorable resistance implications of PI- versus NNRTI-based first line therapy, widespread use of PI-based first-line therapy is not warranted at this time, due to resource limitations and predicted increased risk of resistance-related failure of NNRTI/NRTI second-line regimens. PI-based first-line therapy could be reconsidered when antiretroviral agents from other classes become available for second-line regimens in resource-limited settings.
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    ABSTRACT: Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success.
    The Journal of Infectious Diseases 06/2013; 207 Suppl 2:S63-9. · 5.85 Impact Factor
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    ABSTRACT: To compare WHO first-line antiretroviral therapy (ART) with nonnucleoside reverse transcriptase inhibitors (NNRTI)-based regimen with a boosted protease inhibitor (bPI) regimen in a resource-limited setting regarding treatment outcome and emergence of drug resistance mutations (DRMs).
    AIDS (London, England) 05/2014; 28(8):1143-1153. · 4.91 Impact Factor


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Jun 1, 2014